Our long-range research interest is to understand adult sensory cortical plasticity. To this end, we found that application of neurotrophins to the adult somatosensory sensory cortex resulted in rapid (minutes) and dramatic changes in both amplitude and areal extent of evoked sensory response to tactile stimulation. These results suggest a surprising new role for neurotrophins in mediating rapid adult cortical plasticity. The proposed experiments will examine the role and mechanism by which the neurotrophin nerve growth factor (NGF) induces such rapid cortical plasticity. We will test the hypothesis that NGF is part of a cortex-to-basal forebrain cholinergic system (BFCS) feedback mechanism that can induce very rapid cortical plasticity. Specifically, NGF may be released by activated cortical neurons that, in turn, enhance the cholinergic release from terminals located on BFCS projections in the cortex. If supported, such a hypothesis would provide a mechanism that would explain how the cortex could self-regulate its own plasticity. For example, such self-regulation of plasticity may provide a means for the cortex to enhance rapidly the effects of sensory input that has important behavioral value. Indeed, the BFCS has been implicated in enhancing the behavioral importance of a sensory stimulus by inducing cortical plasticity. Experiments are designed to prove that cortex-to-BFCS feedback system, via the action of NGF on the BF CS projections in the cortex, is both necessary and sufficient to elicit rapid cortical plasticity. Our research strategy is to identify the NGF/ACh projections to the somatosensory cortex, to stimulate that system and then to eliminate its function. The results of the proposed experiments will be quantified by using in vivo high-resolution imaging of cortical activity. If our hypothesis is verified, it will add a fundamental insight to the cellular and molecular mechanisms by which the adult cortex can regulate its own plasticity and to the nature of cortical plasticity in general. As cortical plasticity is implicated in many fundamental processes of the brain in general and the cortex in particular, ranging from recovery after injury and sensory deprivation to learning and memory, there is a growing need to better understand the mechanisms underlying such plasticity.